Green Flu

Like many of the more recent incarnations of zombie movies, videogames, 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 plotline).

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, as other more "classical" zombie viruses spread (though the "churchguy" mentions he was bitten and shortly thereafter turned). It appears that the survivors are immune to the virus. It is not explained what factors certain victims become simple zombies, while others become boss infected.

However, 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 deceased (and presumably infected) corpse. He mentions that he hasn't ever seen anything like it before, but it doesn't seem to hurt him in any immediate way, and neither does smearing it on Francis' jacket. This is most likely Boomer bile as 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".

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.

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 biohazard tapes crossing the hallways and rooms near the quarantine room that also has several biohazard posters stuck to the glass wall of the room. Inside is a corpse of 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.