Green Flu

Like many of the more recent incarnations of zombie movies, video games, and books, the Infected are zombie-like creatures caused by an unknown, as-yet-unnamed infection. Promotional materials from multiple sources state that the virus is a mutated strain of the rabies virus. There has been much speculation as to the cause of the infection, or whether or not its origin will even have any relevance at all in the plot of the game (especially if, as some have speculated, each campaign of the game is a separate plot line).

Valve games typically contain stories that are expressed through exploring the world and interacting with its inhabitants rather than from watching lengthy cut-scenes or reading explanatory paragraphs out of the game manuals. From what we've seen of the game so far, this seems to be the case in Left 4 Dead as well. Graffiti covers many walls of the game, often containing messages to separated loved ones, foreboding messages of warning, and, most interestingly, past survivors' own explanations for the infection, varying from government conspiracy to alien plot.

Means of infection
The intro movie to the game begins with the cryptic statement "2 WEEKS AFTER FIRST INFECTION," implying that a single individual was once infected with an unknown virus of some sort, and the virus spread from there. What's not immediately clear, however, is the means of spreading the infection. The infected don't seem necessarily ready to bite players (although, strictly speaking, story-wise the Survivors would never get bitten), as other more "classical" zombie viruses spread (though the "church guy" mentions he was bitten and shortly thereafter turned). During one of several possible dialogues with the "church guy", Bill says something to the effect of "We're immune and we're tired, let us in", providing evidence that the four Survivors are immune and cannot change into zombies. The Infected appear to favor the immediate death of the Survivors rather than infection through biting or some other method, which might mean they display some ability to detect immunity or still have some small sense of self-preservation. Also, if the infection has regressed the Infected's mental abilities to a base desire to spread the virus, and it was only contagious by biting or clawing, it would possibly explain why the Infected do not choose to make use of the weapons and ammunition found in the various safe houses and during the finale of each chapter. It is not explained under which factors certain victims become simple zombies, while others become boss infected, though it is possible that there are different strains of the virus or that it mutates.

Immediately after the aforementioned intro card for the opening cut scene, Bill is seen discovering a viscous, bright green substance in or on (it's difficult to discern) a dead (and presumably infected) body. He mentions that he's never seen anything like it before, but it doesn't seem to hurt him in any immediate way, and neither does smearing it on Francis' vest (which annoys him). This is most likely Boomer bile (a Boomer corpse is seen in the background if observed closely enough). The substance was said to reek, and Bill claims that the liquid was a sign that the infected were "changing." What this may mean is unknown, but it may imply that the infected are still in the process of mutating, and that all the changes the virus will cause to its host is as of yet unknown. This could mean that the boss infected were just starting to develop and this was the Survivors first encounter with one. This is backed up by how Zoey approaches what she assumes is a survivor crying, despite the obvious signs of her being a Witch, implying that she has never encountered one before. However, it seems that Bill does recognize the Witch, ordering Zoey to shut off her light and back away. The Witch is also mentioned in some graffiti in a safe house, yet isn't named by the person that wrote it.

CEDA posters in the airport suggest that the infection is related to livestock, and later, towards the end of the Blood Harvest campaign, the player will encounter several deceased cows, neatly stacked atop one another. The cows typically have the skin around their skull missing, but the rest of their body is untouched for some reason. There is writing in a safe room within the No Mercy campaign that disregards the CEDA's safety step that tells Survivors to treat the Infection as though it were airborne. Also, being a strain of rabies, it's very probable that the Infection's primary form of spreading is through biting.

Length of time it takes to turn
Though there has been no official confirmation by Valve on how long it takes for an infected person to turn, there is a conversation on the wall of the Rooftop Finale's starting safe house in graffiti. There a number of unnamed Survivors wrote down the time they think it takes to change. One had seen someone turn in four days, and more people come along to "correct" each other until the last person writes that they saw someone turn in 5 minutes. It's possible that the time it takes varies from person to person, as Church Guy claims to have been bitten an hour before the Survivors make it to his safe house.

Possible Original Victim
In the last parts of No Mercy there is a quarantine room on the fourth floor of mercy hospital around the corner from the elevator that is surrounded by yellow bio hazard tapes crossing the hallways and rooms near the quarantine room that also has several bio hazard posters stuck to the glass wall of the room. Inside is a corpse of a man lying face down in a hospital gown with blood around his mouth. This seems to hint that he was at least one of the first, if not the first, in the area to be infected, maybe even making him the original victim of the infection.

Also noteworthy is the fact that bags of IV fluid (which looks like blood) on racks near beds at Mercy Hospital have the word CONTAMINATED stamped in bold red print across their label.

Trivia

 * On the upper floor of The Town's beginning safe room, there's a poster with a bed and the words, "Don't let the Infected bite." This may further suggest that the Infection is spread mainly through biting.


 * In the Hospital Stage of No Mercy, an X-Ray of a hand missing a thumb, much like the game's token image, can be found in various different rooms. If this person became Infected, they made it to the Apartments area of No Mercy as shown in the opening cinematic.


 * Through various conversations left as graffiti on the walls, it has been noted that other survivors have noticed that the infected can communicate to some level or at least utter words.


 * According to graffiti conversations between survivors in the game, speculations of the origins of the virus range from the military to space aliens as seen here.


 * According to various graffiti, signs and conversations, some people are naturally immune to the infection, such as the four survivors. This may imply that the Infection can only affect certain strands of DNA, which may suggest the Infection was originally a failed biological warfare project. Or the opposite may be true, in that the infection cannot, for unknown reasons, affect certain people's DNA, which also implies that a cure can be made.  Of course, this is all only speculation among fans, based on various hints littered throughout the game.


 * As the cause of the Infection is unknown, some players have taken to calling it "Zombie Cancer" as a joke explanation, a reference to a Newgrounds cartoon called Awesome Center Redux.